tbuckley/cabot-search huggingface dataset:
PD-12 Transcriptome-based classification to predict FOLFIRINOX response in a real-world metastatic pancreatic cancer cohort
Authors: M. Lansbergen, M. Dings, P. Manoukian, G. Hooijer, A. Farina Sarasqueta, J. Verheij, J. Koster, D. Zwijnenburg, J. Wilmink, E. Cuppen, H. Bloemendal, J. Medema, F. Dijk, H. van Laarhoven, M. Bijlsma
Journal: Annals of Oncology (2023)
P-79 Feasibility and toxicity of hypofractionated radiotherapy (5x5 Gy) with a simultaneous integrated boost (5x6 Gy) in locally advanced rectal cancer: 2023 update
Authors: M. Temnyk, K. Pędziwiatr, M. Gidzińska, M. Chojnacka, L. Wyrwicz
Journal: Annals of Oncology (2023)
P-414 Gastric cancer risk factors knowledge in Mexican population. LEGACy 3A
Authors: E. Ruiz-Garcia, E. Fernandez-Figueroa, A. Moreno Avedaño, U. Coquis Navarrete, J. Falcon, D. Ramirez Manriquez, C. Garcia Rios, S. Velasco Fuentes, I. Cardenas-Delgado, A. Leon Takahashi, C. Diaz, N. Ortiz-Olvera, T. Fleitas Kanonnikoff
Journal: Annals of Oncology (2023)
P-268 Using 16S rRNA gene sequencing to investigate the composition of Fusobacterium-associated microbiota and its impact on outcome in rectal cancer
Authors: S. Napoli, G. Serna, J. Hernando, F. Ruiz-Pace, L. Alonso, R. Fasani, A. García Álvarez, S. Landolfi, R. Comas, J. Jimenez, A. Santiago, E. Élez, I. Baraibar, J. Tabernero, R. Dientsmann, J. Capdevila, P. Nuciforo
Journal: Annals of Oncology (2023)
SO-5 Futibatinib in patients with FGFR2-rearranged intrahepatic cholangiocarcinoma: Responder analyses of efficacy and safety from the phase 2 FOENIX-CCA2 study
Authors: A. Hollebecque, L. Goyal, F. Meric-Bernstam, J. Furuse, M. Moehler, A. Vogel, X. Liu, V. Wacheck, J. Bridgewater
Journal: Annals of Oncology (2023)
SO-29 Clinical characteristics, efficacy, and safety in patients receiving second- or third-line encorafenib plus cetuximab (E+C) vs control for metastatic colorectal cancer (mCRC): BEACON CRC post hoc analysis
Authors: J. Tabernero, E. Van Cutsem, T. Yoshino, R. Yaeger, H. Wasan, J. Desai, F. Ciardiello, B. Alkuzweny, X. Zhang, C. Guenzil, S. Kopetz
Journal: Annals of Oncology (2023)
SO-3 Clinical relevance and actionability of BRAF alterations in advanced biliary tract cancer: Preliminary results from the multicenter B-REAL study
Authors: M. Niger, F. Nichetti, S. Murgioni, V. Zanuso, C. Bagalà, G. Masi, E. Gusmaroli, E. Perissinotto, A. De Rosa, R. Balsano, M. Bensi, V. Genovesi, G. Pruneri, L. Rimassa, L. Salvatore, C. Vivaldi, F. Bergamo, F. Pietrantonio, F. de Braud, S. Lonardi
Journal: Annals of Oncology (2023)
P-161 MiR181c/d regulates sensitivity to cisplatin/gemcitabine by targeting SIRT1 in cholangiocarcinoma
Authors: M. Salati, F. Piscopo, B. Anna, L. Evangelista, D. Limongello, P. Pisapia, A. Spallanzani, F. Gelsomino, B. Riccò, B. Medici, L. Reggiani Bonetti, G. Troncone, M. Dominici, F. Brunella, P. Carotenuto
Journal: Annals of Oncology (2023)
O-8 Somatic and germline heterogeneity across colorectal cancer patient characteristics: Implications for early cancer detection
Authors: J. Weitzel, P. Srinivasan, B. Gutman, S. Bristow, H. Wu, R. Salari, R. Swenerton, T. Kawli, A. Aleshin, M. Rabinowitz, B. Zimmermann, B. Mitchell, J. Reiter
Journal: Annals of Oncology (2023)
P-128 Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer
Authors: I. Motoo, T. Ando, S. Kajiura, M. Sakumura, Y. Ueda, A. Ueda, N. Suzuki, N. Nakada, A. Hosokawa, I. Yasuda
Journal: Annals of Oncology (2023)
P-164 Efficacy and safety of dostarlimab in UK-specific patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) or DNA polymerase epsilon, catalytic subunit (POLƐ)-mutated solid tumours in the GARNET study
Authors: L. Samuel, R. Miller, P. Ross, T. Arkenau, G. Antony, J. Veneris, J. Rule, N. Starling
Journal: Annals of Oncology (2023)
P-156 Efficacy and safety of cadonilimab combined with FLOT regimen as a neoadjuvant therapy for locally advanced gastric/gastroesophageal junction adenocarcinoma: A prospective, multicenter, open-label, single-arm phase II study
Authors: B. Long, H. Zhou, D. Wei, T. Yang, N. Chai, Z. Yu, H. Yang, X. Guan, W. Zhang, S. Chen, L. Zhou, X. Jiang, W. Shi, Z. Huang, J. Zhu, C. Luo, J. Mao, C. Dong, Z. Jiang, X. Zhao, D. Zhao, Z. Jiao
Journal: Annals of Oncology (2023)
P-162 Preliminary results of the feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): A retrospective exploratory study
Authors: J. Huang, J. Liu, Y. Hong, J. Xia, P. Lu, Z. Chang, G. Zhang, X. Ma, W. Liang
Journal: Annals of Oncology (2023)
P-354 A single arm phase II trial of capecitabine and erlotinib in patients with advanced hepatocellular carcinoma after first-line failure (CAPER- HCC study)
Authors: S. Srinivas, P. Bhargava, A. Ramaswamy, S. Mandavkar, C. Nashikkar, D. Naughane, V. Ostwal
Journal: Annals of Oncology (2023)
SO-22 Gut microbiome composition as predictor of the efficacy of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in metastatic colorectal cancer: A translational analysis of the AtezoTRIBE study
Authors: F. Marmorino, G. Piccinno, D. Rossini, F. Ghelardi, S. Murgioni, L. Salvatore, V. Nasca, C. Antoniotti, F. Daniel, F. Schietroma, V. Conca, C. Alves Costa Silva, E. Tamburini, S. Tamberi, A. Passardi, M. Carullo, L. Antonuzzo, R. D'Onofrio, L. Zitvogel, C. Cremolini, L. Derosa
Journal: Annals of Oncology (2023)
P-106 The neoadjuvant rectal (NAR) score application in the context of total neoadjuvant treatment with chemo-immuno-radiation for locally advanced rectal cancer: Data from the phase II Averectal study
Authors: L. Chehade, R. Turfa, A. Machmouchi, J. Kattan, S. Temraz, K. Alqasem, R. Amarin, T. Al Awabdeh, I. Mohamad, F. Daoud, M. Al Masri, A. Dabous, A. Hushki, O. Jaber, M. Charafeddine, M. Al Darazi, A. Shamseddine
Journal: Annals of Oncology (2023)
P-123 CD73high biliary tract cancer (BTC) is a molecularly defined subtype with distinct clinical implications
Authors: M. Salati, B. Anna, C. O'Rourke, F. Piscopo, L. Evangelista, P. Pisapia, B. Riccò, A. Spallanzani, F. Gelsomino, U. Malapelle, L. Reggiani Bonetti, J. Andersen, G. Troncone, M. Dominici, F. Brunella, P. Carotenuto
Journal: Annals of Oncology (2023)
O-3 Additional data from the KEYNOTE-859 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer
Authors: L. Wyrwicz, D. Oh, P. Weber, Y. Bai, M. Ryu, J. Lee, F. Rivera, G. Vasconcelos Alves, M. Garrido, K. Shiu, M. Gonzalez Fernandez, J. Li, M. Lowery, T. Çil, F. Cruz, S. Qin, L. Yin, S. Bordia, P. Bhagia, S. Rha
Journal: Annals of Oncology (2023)
P-150 Hispanic/Latino patients with metastatic gastric adenocarcinoma: Impact of single metastasis in overall survival
Authors: C. Diaz, H. Lopez Basave, S. Miyagui Adame, B. Carbajal-López, A. Albarran, J. Ramos Amador, D. Guerra Figueroa, G. Calderillo-Ruiz
Journal: Annals of Oncology (2023)
P-30 Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab-based therapy – final results of the phase II RE-ExPEL study
Authors: T. Goetze, A. Stein, S. Lorenzen, T. Habibzada, E. Goekkurt, P. Herhaus, D. Sookthai, T. Brulin, K. Ihrig, C. Pauligk, S. Al-Batran
Journal: Annals of Oncology (2023)
P-279 Adjuvant chemotherapy for patients with stage III colon cancer, three months vs six months. A single centre experience
Authors: G. Martin-Montalvo, D. Martinez Perez, I. Ruiz-Gutierrez, M. Alameda, A. Rueda-Lara, J. Peña, D. Jimenez-Bou, D. Viñal, J. Garcia-Cuesta, J. Pedregosa Barbas, N. Rodríguez-Salas, J. Feliu
Journal: Annals of Oncology (2023)
PD-21 Exploring the prognostic and predictive impact of genomic loss of heterozygosity (LOH) in metastatic colorectal cancer (mCRC) patients
Authors: M. Carullo, M. Germani, R. Moretto, V. Conca, A. Minelli, M. Giordano, R. Bruno, M. Prisciandaro, S. Lonardi, M. Bensi, G. Tonini, M. Palladino, M. Ramundo, S. Tamberi, C. Antoniotti, D. Rossini, C. Ugolini, F. Marmorino, G. Fontanini, C. Cremolini
Journal: Annals of Oncology (2023)
P-406 Association between mutated RAS status and microvascular density (MVD) in advanced colorectal cancer
Authors: H. Yaïche, F. Letaief-Ksontini, N. Ben Jemii, A. Jaballah-Gabteni, I. Ben Ayed, D. Wider, H. Guettiti Tounsi-Kettiti, S. Boubaker
Journal: Annals of Oncology (2023)
P-5 A soluble resistance related calcium binding protein (sorcin) up-regulates in the multi-drug resistant advanced gastric cancer patients
Authors: S. Ghosh, T. Mistry, R. Pal, P. Sahoo, S. Mahata, S. Sarkar, T. Choudhury, R. Banerjee, J. Chakrabarti, K. Mukherjee, N. Alam, S. Mandal, V. Nasare
Journal: Annals of Oncology (2023)
SO-8 Predictive values of blood-based RNA signature for the FOLFIRINOX/FOLFOX response in advanced pancreatic cancer
Authors: D. Piquemal, F. Noguier, B. Bournet, F. Ghiringhelli, F. Pierrat, C. Canivet, A. Bertaut, R. Bruno, L. Evesque, A. Gamez, J. Cros, C. Lepage, E. François, C. Louvet, J. Vincent, A. Hennequin, L. Bengrine, P. Afchain, I. Trouilloud, J. Bachet
Journal: Annals of Oncology (2023)
P-170 The MATTERS trial: A first-in-human study of whole-body hyperthermia in advanced solid cancer patients
Authors: I. Gorbaslieva, R. Dankerlui, D. Ysebaert, V. Saldien, T. Vandamme, L. Brancato, O. Rudenko, L. Van den Bossche, J. Van den Bossche, K. Van den Cruys, J. Bogers, M. Peeters
Journal: Annals of Oncology (2023)
P-330 ERBB2 mutations in metastatic colorectal cancer: From clinicopatholgical features to potential treatment implications in a real-world cohort
Authors: C. Vaghi, G. Mauri, A. Amatu, F. Tosi, E. Bonazzina, K. Bencardino, S. Siena, A. Sartore Bianchi
Journal: Annals of Oncology (2023)
P-137 Phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced cholangiocarcinoma (CCA) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations
Authors: J. Harding, C. Perez, S. Kato, M. Sharma, B. Garmezy, C. Quah, B. Tam, P. Severson
Journal: Annals of Oncology (2023)
P-146 Efficacy and safety of FLOT combined with apatinib and sintilimab as a neoadjuvant therapy regimen for locally advanced gastric or gastroesophageal junction adenocarcinoma: An open-lable, single-arm, phase II study
Authors: H. Zhou, B. Long, Z. Yu, J. Zhu, H. Yang, W. Zhang, X. Guan, G. Zhang, L. Li, C. Luo, H. Cao, S. Zhang, S. Chen, Q. He, S. Gan, L. Zhou, X. Jiang, W. Shi, Z. Huang, J. Mao, C. Dong, Z. Jiao
Journal: Annals of Oncology (2023)
P-213 Prognostic biomarkers in patients with oesophago-gastric cancer treated with immunotherapy
Authors: E. Terán Brage, M. Garijo Martínez, P. Díaz Sánchez, None Á López Gutiérrez, D. Morchón Araujo, Y. López Mateos, M. Navarro Martín, M. García García, E. Del Barco Morillo, E. Fonseca Sánchez, R. Vidal Tocino
Journal: Annals of Oncology (2023)
P-9 Multivariate prognostic models for patients with stage I and II colon carcinoma: A STROBE-compliant retrospective cohort study
Authors: L. Onate-Ocana, R. Herrera-Goepfert, A. Avilés-Salas, C. Cortés, S. González-Trejo, J. Carrillo, E. Ruiz-Garcia, F. Ochoa-Carrillo, V. Aiello-Crocifoglio, C. García-Cuéllar
Journal: Annals of Oncology (2023)
SO-28 FOLFOXIRI plus bevacizumab and atezolizumab as upfront treatment of unresectable mCRC patients: Updated and overall survival results of the phase II randomized AtezoTRIBE study
Authors: C. Antoniotti, D. Rossini, F. Pietrantonio, L. Salvatore, F. Marmorino, M. Ambrosini, S. Lonardi, M. Bensi, R. Moretto, S. Tamberi, I. Toma, A. Passardi, M. De Grandis, V. Conca, M. Palermo, A. Cappetta, A. Catteau, L. Boni, J. Galon, C. Cremolini
Journal: Annals of Oncology (2023)
P-22 Frequency of dihydropyrimidine dehydrogenase (DPD) deficiency detection and adverse events in patients receiving fluoropyrimidine-based therapy in a pancreatic and biliary tract cancer cohort
Authors: E. Wilson, P. Monaghan, J. Gleeson, A. Lamarca, R. Hubner, J. Valle, M. McNamara
Journal: Annals of Oncology (2023)
P-273 Genomic signatures associated with aggressive histology and decreased overall survival in neuroendocrine malignancies
Authors: N. Farha, W. Wei, P. Mundi, S. Krishnamurthi, S. Steele, S. Kamath, E. Gorgun, D. Liska, B. Estfan, A. Khorana, B. Laderian
Journal: Annals of Oncology (2023)
P-55 Obstructive gastric and gastroesophageal junction cancer predicts worse survival in curatively treated patients – analysis from a tertiary care center in India
Authors: A. Simha, M. Imaduddin, S. G, R. K, M. Sultania, H. Nayak, M. Panigrahi, D. Muduly, M. Kar
Journal: Annals of Oncology (2023)
P-336 Neoadjuvant chemotherapy of the mFOLFIRINOX in the treatment of resectable pancreatic cancer
Authors: D. Kantieva, I. Bazin, D. Podluzhnyi, M. Manukyan, Y. Chikhareva, A. Polyakov, N. Kudashkin, A. Kotelnikov, A. Petrosyan, I. Pogrebnyakov, E. Moroz, A. Tryakin
Journal: Annals of Oncology (2023)
P-371 Docetaxel-based perioperative chemotherapy in gastric and gastroesophageal (GEJ) adenocarcinomas – a real world experience from a tertiary cancer centre in India
Authors: A. Khan, A. Bonda, V. Muddu, I. Siripurapu, R.G. V, K. Bhattacharya, N. D
Journal: Annals of Oncology (2023)
P-391 Perioperative chemotherapy for operable gastro-esophageal or gastric cancer: Anthracycline triplets versus FLOT
Authors: C. van der Zijden, J. Geerts, P. van der Sluis, M. Spaander, G. Nieuwenhuijzen, C. Rosman, H. van Laarhoven, R. Verhoeven, B. Wijnhoven, S. Lagarde, B. Mostert
Journal: Annals of Oncology (2023)
SO-15 Four-year overall survival update from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
Authors: B. Sangro, S. Chan, R. Kelley, G. Lau, M. Kudo, W. Sukeepaisarnjaroen, E. De Toni, J. Furuse, Y. Kang, P. Galle, L. Rimassa, A. Heurgué, V. Tam, T. Dao, S. Thungappa, V. Breder, Y. Ostapenko, M. Reig, M. Makowsky, C. Gupta, A. Negro, G. Abou-Alfa
Journal: Annals of Oncology (2023)
O-12 NCI9673 (Part B): A multi-institutional ETCTN randomized phase II study of nivolumab with or without ipilimumab in refractory, metastatic squamous cell carcinoma of the anal canal
Authors: V. Morris, K. Ciombor, B. Polite, S. Mukherjee, J. Krauss, A. Shields, O. Aranha, J. Hays, S. Kazmi, B. Weinberg, A. Benson, C. Lieu, S. Iqbal, H. Hochster, L. Xiao, C. Eng
Journal: Annals of Oncology (2023)
P-314 mIR-26A and mIR-335-5p as clinical biomarkers in Latin American patients with colon cancer: Preliminary results
Authors: B. Carbajal-López, G. Calderillo-Ruiz, E. Madrigal-Santillan, J. Coronel Herández, A. Martínez Gutiérrez, O. Millan Catalan, C. Diaz, L. Saul, C. Perez Plasencia, E. Perez Yepez
Journal: Annals of Oncology (2023)
P-409 Outcomes of patients with unresectable hepatocellular carcinoma who developed an infection while receiving atezolizumab
Authors: A. Esmail, J. Xu, E. Burns, K. Gee, C. Wiechmann, Y. Zhang, R. Kieser, Z. Gong, G. Umoru, S. Shah, K. Sun, K. Heyne, M. Abdelrahim
Journal: Annals of Oncology (2023)
P-142 Completion of genetic testing and incidence of pathogenic germline mutation among patients with early-onset colorectal cancer, a single institution retrospective analysis
Authors: M. Storandt, K. Rogen, A. Iyyangar, J. Mitchell, J. Hubbard, F. Sinicrope, A. Jatoi, A. Mahipal, Q. Shi, Z. Jin
Journal: Annals of Oncology (2023)
P-76 Genomic and transcriptomic characterization of pancreatic neuroendocrine tumors reveals novel therapeutic candidates
Authors: A. Azmi, Z. Mahdi, S. Bannoura, M. Al-Hallak, M. Uddin, H. Khan, I. Muqbil, R. Mohammad, H. Chen, P. Philip, B. El-Rayes
Journal: Annals of Oncology (2023)
P-129 Necessity and safety of simultaneous cholecystectomy during gastric surgery in patients with asymptomatic cholelithiasis: A systematic review and meta-analysis
Authors: T. Jiang, H. Zhang, X. Yin, Z. Cai, Z. Zhao, M. Mu, B. Liu, C. Shen, B. Zhang, Y. Yin
Journal: Annals of Oncology (2023)
P-13 Management of metastatic colorectal cancer in patients ≥70 years: A single-center experience
Authors: F. Huemer, C. Dunkl, G. Rinnerthaler, K. Schlick, R. Heregger, K. Emmanuel, D. Neureiter, E. Klieser, M. Deutschmann, F. Roeder, R. Greil, L. Weiss
Journal: Annals of Oncology (2023)
P-290 Treatment sequences and locoregional therapies for patients with carcinoid and refractory carcinoid syndrome. A multicentric cohort analysis
Authors: A. Oviedo, R. Luca, A. Rodriguez, F. Waisberg, C. Ypa, F. Esteso, S. Iseas, M. Carballido, J. Maquieira, E. Roca, M. Chacón, G. Mendez, J. O’Connor
Journal: Annals of Oncology (2023)
P-131 Evaluation of predictive factors of toxicity of chemotherapy with FOLFIRINOX in patients treated for pancreatic adenocarcinoma
Authors: R. Eid, A. Tarabay, P. Decazes, C. David, F. Kerbage, J. Zeghondy, L. Antoun, C. Smolenschi, A. Fuerea, M. Valéry, V. Boige, M. Gelli, L. Tselikas, J. Durand Labrunie, Y. Belkouchi, M. Ducreux, N. Lassau, A. Hollebecque
Journal: Annals of Oncology (2023)
P-351 Colon cancer in young patients – real-world data from a single center review
Authors: M. Montenegro, A. Spencer, J. Leão, I. Furtado, R. Ferreira, R. Escaleira, F. Verdasca, M. Seladas, V. Fernandes, L. Gil, J. Ferreira, I. Guerreiro, R. Luz
Journal: Annals of Oncology (2023)
P-147 Latin American women with gastric adenocarcinoma and ovarian metastasis: Therapeutic approaches and overall survival
Authors: G. Calderillo-Ruiz, J. Cervantes Bojalil, B. Carbajal-López, M. Herrera, S. Zilli-Hernandez, A. Takahashi, P. Morales Esponda Mendoza, C. Diaz
Journal: Annals of Oncology (2023)
P-174 Outcomes in local gastric cancer resected without neoadjuvant therapy: A descriptive study
Authors: E. Bujons Buscarons, C. Montañes Ferrer, L. Llavata Marti, J. Sabaté Ortega, C. Codony Bassols, A. García Velasco, M. Pujadas de Palol, X. Hernández-Yagüe, R. Guardeño Sanchez
Journal: Annals of Oncology (2023)
Physicians' Attitudes Toward Using Deception to Resolve Difficult Ethical Problems
Authors: Dennis H. Novack
Journal: JAMA (1989)

To assess physicians' attitudes toward the use of deception in medicine, we sent a questionnaire to 407 practicing physicians. The questionnaire asked for responses to difficult ethical problems potentially resolvable by deception and asked general questions about attitudes and practices. Two hundred eleven (52%) of the physicians responded. The majority indicated a willingness to misrepresent a screening test as a diagnostic test to secure an insurance payment and to allow the wife of a patient with gonorrhea to be misled about her husband's diagnosis if that were believed necessary to ensure her treatment and preserve a marriage. One third indicated they would offer incomplete or misleading information to a patient's family if a mistake led to a patient's death. Very few physicians would deceive a mother to avoid revealing an adolescent daughter's pregnancy. When forced to make difficult ethical choices, most physicians indicated some willingness to engage in forms of deception. They appear to justify their decisions in terms of the consequences and to place a higher value on their patients' welfare and keeping patients' confidences than truth telling for its own sake. (<i>JAMA</i>. 1989;261:2980-2985)
A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme
Authors: F.M. TATNALL, J.K. SCHOFIELD, I.M. LEIGH
Journal: British Journal of Dermatology (2006)

Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir-treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.
Lipocalin 10 is essential for protection against inflammation-triggered vascular leakage by activating LDL receptor-related protein 2-slingshot homologue 1 signalling pathway
Authors: Hongyan Zhao, Peng Wang, Xiaohong Wang, Wa Du, Hui-Hui Yang, Yueying Liu, Shu-Nan Cui, Wei Huang, Tianqing Peng, Jing Chen, Chen Gao, Yigang Wang, Sakthivel Sadayappan, Chengen Ma, Yanbo Fan, Chunting Wang, Guo-Chang Fan
Journal: Cardiovascular Research (2023)

Abstract Aims Systemic inflammation occurs commonly during many human disease settings and increases vascular permeability, leading to organ failure, and lethal outcomes. Lipocalin 10 (Lcn10), a poorly characterized member of the lipocalin family, is remarkably altered in the cardiovascular system of human patients with inflammatory conditions. Nonetheless, whether Lcn10 regulates inflammation-induced endothelial permeability remains unknown. Methods and results Systemic inflammation models were induced using mice by injection of endotoxin lipopolysaccharide (LPS) or caecal ligation and puncture (CLP) surgery. We observed that the expression of Lcn10 was dynamically altered only in endothelial cells (ECs), but not in either fibroblasts or cardiomyocytes isolated from mouse hearts following the LPS challenge or CLP surgery. Using in vitro gain- and loss-of-function approaches and an in vivo global knockout mouse model, we discovered that Lcn10 negatively regulated endothelial permeability upon inflammatory stimuli. Loss of Lcn10 augmented vascular leakage, leading to severe organ damage and higher mortality following LPS challenge, compared to wild-type controls. By contrast, overexpression of Lcn10 in ECs displayed opposite effects. A mechanistic analysis revealed that both endogenous and exogenous elevation of Lcn10 in ECs could activate slingshot homologue 1 (Ssh1)-Cofilin signalling cascade, a key axis known to control actin filament dynamics. Accordingly, a reduced formation of stress fibre and increased generation of cortical actin band were exhibited in Lcn10-ECs, when compared to controls upon endotoxin insults. Furthermore, we identified that Lcn10 interacted with LDL receptor-related protein 2 (LRP2) in ECs, which acted as an upstream factor of the Ssh1-Confilin signalling. Finally, injection of recombinant Lcn10 protein into endotoxic mice showed therapeutic effects against inflammation-induced vascular leakage. Conclusion This study identifies Lcn10 as a novel regulator of EC function and illustrates a new link in the Lcn10-LRP2-Ssh1 axis to controlling endothelial barrier integrity. Our findings may provide novel strategies for the treatment of inflammation-related diseases.